Correlation Study Of Exosomes Derived From Colorectal Cancer Regulating Fibroblast

Our study intends to explore the effects of lnc RNA HNF1-AS1 derived from CRC exosomes in normal fibroblast activation and CRC metastasis.Firstly,a series of in vitro and in vivo experiments were performed to elucidate the effects of lnc RNA HNF1A-AS1 derived from different CRC exosomes in fibroblast activation and CRC liver metastasis.Next,the role of activated fibroblasts in the biological function of CRC cells and the clinical value of lnc RNA HNF1A-AS1 derived from exosomes of CRC serum were investigated through in vitro function assays and ROC curves.The results showed that the exosomes were successfully extracted from CRC cells supernatants or serum and the expression of lnc RNA HNF1A-AS1 was higher in exosomes of highly metastatic CRC.The expression of FAP and α-SMA in fibroblasts treated with exosomes released from high metastatic CRC cells was significantly higher than that from the control group,as well as,the ability of migration and invasion was significantly enhanced.Lnc RNA HNF1A-AS1 silencing inhibited the expression of FAP and α-SMA in fibroblasts as well as the ability of migration and invasion.Compared with the control group,the animal model of CRC liver metastasis that injected high-metastatic CRC cell exosomes through the tail vein had larger liver metastases and higher α-SMA expression in the metastases.However,the results of the CRC liver metastasis model implanted silencing lnc RNA HNF1A-AS1 through the spleen were the opposite.Activated fibroblasts accompany the activation of the Notch pathway and promote the migration and invasion of CRC cells.However,DAPT,a Notch pathway inhibitor,can attenuate the activation of normal fibroblasts and the migration and invasion of CRC cells.Compared with healthy groups and non-metastatic CRC patients,the expression of lnc RNA HNF1A-AS1 in serum exosomes derived from metastatic CRC patients was higher.Compared with the ROC curve of CEA,the AUC,sensitivity,and specificity of lnc RNA HNF1A-AS1 derived from serum exosomes in CRC patients were improved.In conclusion,high metastatic CRC cells regulate and interact with normal fibroblasts by secreting exosomes containing lnc RNA HNF1A-AS1,and then promote CRC liver metastasis.Lnc RNA HNF1A-AS1 in serum exosomes of CRC patients may become a novel serum marker for colorectal cancer diagnosis.